Regulation of hematopoiesis by retinoid signaling.

The discovery that retinoic acid efficiently stimulates the terminal differentiation of granulocytic leukemia cells had a major impact on clinical hematology, but has also inspired research into the normal function of the retinoid signaling pathway during hematopoiesis. New animal models and loss-of-function approaches have successfully revealed requirements for the pathway at defined embryonic stages that are relevant for distinct hematopoietic cell populations. For example, novel insight has been gained regarding the function of retinoids in yolk sac hematovascular development, fetal erythropoiesis, T-cell homing, and hematopoietic stem and progenitor cell biology. The lessons learned so far indicate that future development of sophisticated animal models will be needed to fully understand the intricacy and specificity of this complex signaling pathway, but that this effort will be productive and continue to inform both basic and clinical research on many fronts.